Abide’s platform embraces the virtues of covalent inhibition to accelerate drug discovery. We develop small molecule inhibitors of serine hydrolases in diverse therapeutic areas in order to understand and treat disease. Through iterative cycles of activity-based protein profiling (ABPP) and medicinal chemistry, we efficiently evaluate and select novel serine hydrolase inhibitors to progress through our drug discovery engine.
Activity-Based Protein Profiling
Activity-based protein profiling (ABPP) employs chemical probes that covalently react with the active sites of mechanistically related classes of enzymes. For example, the fluorophosphonate warhead shown below reacts with active serine hydrolases. By virtue of this reactivity, the fluorophosphonate probe interrogates the activity-state of all the serine hydrolases in a biological sample (cell line, tissue, or fluid) and enables their visualization and identification by either gel- or mass-spectrometry-based approaches.
From a drug discovery perspective, ABPP offers powerful advantages over more traditional methods, including information about changes in biological activity rather than enzyme abundance, and simultaneous characterization of many enzymes in parallel directly in native biological systems. Several key papers describing ABPP and its applications to drug discovery are referenced in Scientific Publications.
Accelerating Drug Discovery
Abide’s platform specifically targets serine hydrolases, a family of enzymes which has already afforded drugs for treatment of a wide array of human diseases, but which remains under-explored. How does our platform accelerate drug discovery to develop the untapped therapeutic value of serine hydrolase inhibitors?
- Proprietary chemical library designed to interact with serine hydrolases
- Direct assessment of proteome-wide selectivity in vitro and in vivo to efficiently guide lead optimization efforts
- Early integration of in vivo pharmacology into the development process to rapidly prioritize compounds for lead optimization